Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing

Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hyd...

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Main Authors: Yue Zhang, Zheng-Hong Chen, Kun Zhao, Yu-Dong Mu, Kun-Long Li, Zhi-Min Yuan, Zhi-Gang Liu, Le Han, Wei-Dong Lü
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424000346
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author Yue Zhang
Zheng-Hong Chen
Kun Zhao
Yu-Dong Mu
Kun-Long Li
Zhi-Min Yuan
Zhi-Gang Liu
Le Han
Wei-Dong Lü
author_facet Yue Zhang
Zheng-Hong Chen
Kun Zhao
Yu-Dong Mu
Kun-Long Li
Zhi-Min Yuan
Zhi-Gang Liu
Le Han
Wei-Dong Lü
author_sort Yue Zhang
collection DOAJ
description Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds.
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spelling doaj.art-286d6c3c3d624f6cb28b251a525bd1b92024-03-18T04:34:20ZengElsevierMaterials Today Bio2590-00642024-04-0125100975Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healingYue Zhang0Zheng-Hong Chen1Kun Zhao2Yu-Dong Mu3Kun-Long Li4Zhi-Min Yuan5Zhi-Gang Liu6Le Han7Wei-Dong Lü8Department of Pathophysiology, Northwestern University School of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi, 710069, ChinaOncology Department of Integrated Chinese and Western Medicine, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Corresponding author. Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, 309 Yanta West Road, Xi'an, Shaanxi, 710061, China.Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds.http://www.sciencedirect.com/science/article/pii/S2590006424000346Acellular embryoid bodiesHydroxybutyl chitosanDiabetic wound healingMacrophage polarizationComposite hydrogels
spellingShingle Yue Zhang
Zheng-Hong Chen
Kun Zhao
Yu-Dong Mu
Kun-Long Li
Zhi-Min Yuan
Zhi-Gang Liu
Le Han
Wei-Dong Lü
Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
Materials Today Bio
Acellular embryoid bodies
Hydroxybutyl chitosan
Diabetic wound healing
Macrophage polarization
Composite hydrogels
title Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
title_full Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
title_fullStr Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
title_full_unstemmed Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
title_short Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
title_sort acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote m2 macrophage polarization and accelerate diabetic cutaneous wound healing
topic Acellular embryoid bodies
Hydroxybutyl chitosan
Diabetic wound healing
Macrophage polarization
Composite hydrogels
url http://www.sciencedirect.com/science/article/pii/S2590006424000346
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